Objective
To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first‐line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to ...Behçet's disease (BD).
Methods
We conducted an open‐label multicenter study of IFX versus ADA for BD‐related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first‐line biologic agent based on physician and patient agreement. Patients received 3–5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4–8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups.
Results
The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best‐corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042).
Conclusion
Although both IFX and ADA are efficacious in refractory BD‐related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow‐up.
The objective of the present study was to assess the efficacy of apremilast (APR) in the management of refractory oral and/or genital ulcers in patients with Behçet's disease (BD).
National ...multicentre open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated.
We included 51 patients (35 women/16 men; mean age 44.7±13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n=19) or genital (n=2) aphthous ulcers or both (n=30). Other manifestations found at APR onset were arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis induced by TNF-α-inhibitors (n=2), ileitis (n=2), deep venous thrombosis (n=2), leg ulcers (n=1), erythematosus and scaly skin lesions (n=1), fever (n=1), unilateral anterior uveitis (n=1) and neuro Behçet (n=1). After a mean follow-up of 8.5±6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable.
APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.
Two main different clinical phenotypes of giant cell arteritis (GCA) have been described, the classic cranial pattern and the extracranial large-vessel (LV) pattern. Since interferon gamma (IFNG) has ...shown to be a pivotal cytokine in the pathophysiology of GCA, our aim was to evaluate for the first time the influence of IFNG and IFNG receptor 1 (IFNGR1) polymorphisms in the different clinical phenotypes of GCA.
Two IFNG polymorphisms (rs2069718 G/A and rs1861493 A/G) and one polymorphism in IFNGR1 (rs1327474 G/A) were genotyped in 191 patients with biopsy-proven cranial GCA, 109 with extracranial LV-GCA and 490 healthy controls. A comparative study was conducted between patients with cranial and extracranial LV-GCA.
No significant differences in genotype, allele, and haplotype frequencies of IFNG polymorphisms were found between GCA patients with the classic cranial pattern and the extracranial LV-GCA pattern. Similar results were found for genotype and allele frequencies of IFNGR1 polymorphism. It was also the case when patients with extracranial LV-GCA were compared with healthy controls.
Our results show that IFNG and IFNGR1 polymorphisms do not influence the clinical phenotype of expression of GCA. Classic cranial GCA and extracranial LV-GCA seem to share a genetic pattern of IFNG pathway.
Since interleukin-6 (IL-6) is a pivotal proinflammatory cytokine implicated in the pathogenesis of giant cell arteritis (GCA), we aimed to determine the potential association of the functional IL6 ...-174 G/C polymorphism with GCA as well as if the single base change variation at the promoter region in the human IL-6 gene may account for differences in the clinical spectrum of GCA between cranial and extracranial large vessel vasculitis (LVV)-GCA.
The IL6 -174 G/C polymorphism (rs1800795) was genotyped in 191 patients with biopsy-proven GCA who had typical cranial manifestations of the disease, 109 patients with extracranial LVV-GCA, without cranial ischaemic manifestations of GCA, and 877 ethnically matched unaffected controls. A comparative study was carried out between patients with cranial and extracranial LVV-GCA and controls.
No significant differences in genotype and allele frequencies of IL6 -174 G/C polymorphism were found between the whole cohort of GCA patients and healthy controls. It was also the case when cranial and extracranial LVV-GCA were compared or when each of these subgroups was compared to controls. Moreover, no significant results in genotype and allele frequencies of IL6 -174 G/C polymorphism were disclosed when the whole cohort of GCA patients were stratified according to the presence of polymyalgia rheumatica, severe ischaemic manifestations, including permanent visual loss and peripheral arteriopathy, and HLA-DRB1*04:01 status.
Our results show that the IL6 -174 G/C polymorphism does not influence the phenotypic expression of GCA.
To determine whether functional vascular endothelial growth factor (VEGF) polymorphisms influence the expression of the clinical phenotype of giant cell arteritis (GCA). We also evaluated whether ...VEGF polymorphism is associated with the development of severe ischaemic manifestations in patients with GCA regardless of the clinical phenotype, classic cranial GCA or predominantly extracranial GCA large vessel vasculitis (LVV).
VEGF rs833061 T/C, rs2010963 G/C and rs3025039 C/T polymorphisms were genotyped in 185 patients with biopsy-proven cranial GCA, 105 with extracranial LVV-GCA and 490 healthy controls. Allelic combinations (haplotypes) of VEGF were carried out. Comparisons were performed between patients with GCA and healthy controls as well as between patients with GCA stratified according to the clinical phenotype and the presence of severe ischaemic manifestations.
No significant differences in genotype, allele, and haplotype frequencies of VEGF were found between patients with GCA and healthy controls as well as between GCA patients with the classic cranial pattern and the extracranial LVV-GCA pattern of the disease. However, the VEGF CGC haplotype (OR= 1.63 1.05-2.53) and the CGT haplotype (OR= 2.55 1.10-5.91) were significantly more frequent in GCA patients with severe ischaemic complications compared to those patients without these complications.
VEGF haplotypes seem to play a role in the development of severe ischaemic manifestations in GCA patients, regardless of the clinical phenotype of expression of the disease.
Clinical improvement following tocilizumab (TCZ) therapy in patients with large-vessel (LVV) giant cell arteritis (GCA) is well established. However, information on TCZ effect on imaging vascular ...activity is limited. We aimed to determine if clinical improvement correlated with reduction of vascular 18F-fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography (PET/CT) scans.
Observational study of patients with refractory LVV-GCA treated with TCZ who had a baseline and a follow-up 18F-FDG-PET/CT scan. For the visual analysis of 18F-FDG vascular uptake, a total vascular score (TVS) was defined, ranging from 0 to 15. Besides, a semiquantitative analysis was performed as a target to background ratio (TBR)= SUVmax thoracic aorta wall/SUVmax aortic vascular pool. The baseline and follow-up TVS and TBR were compared. Clinical and lab¬oratory outcomes were also assessed.
We included 30 patients (24 women/6 men); mean age± standard deviation 65.7± 9.8 years. Baseline PET/CT scans were performed due to active disease at a median interquartile range-IQR of 1.5 0.0-4.0 months before TCZ onset. Following TCZ therapy, 25 (83.33%) patients achieved clinical remission and reduction of 18F-FDG vascular uptake was also observed after a mean ± standard deviation of 10.8±3.7 months. TBR decreased from 1.70 ± 0.52 to 1.48 ± 0.25 (p=0.005) and TVS from 4.97±2.62 to 3.13±1.89 (p< 0.001). However, only 9 (30.0%) patients showed complete normalisation of TBR and only 3 (10%) normalisation of TVS. TBR and TVS showed a good correlation (r=0.576).
Although most of LVV-GCA patients achieve clinical remission after TCZ therapy, less than one-third show normalisation of 18F-FDG vascular uptake.
•HLA typing may help to identify patients with ASSD.•HLA-DRB1*03:01 and HLA-B1*08:01 are predisposition markers of ASSD.•HLA-DRB1*07:01 is a protective allele against ASSD.•HLA-DRB1*03:01 increases ...the risk of developing anti-Jo-1 autoantibodies in ASSD.•Smoking does not seem to influence anti-Jo-1 antibody positivity in ASSD.
To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD).
We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing.
A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P=1.56E–09, odds ratio–OR 95% confidence interval–CI=2.54 1.84–3.50 and 21.4% versus 5.5%, P=18.95E–18, OR 95% CI=4.73 3.18–7.05; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P=0.0003, OR 95% CI=0.48 0.31–0.72). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P=0.001, OR 95% CI=2.54 1.39–4.81). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed.
Our results support the association of the HLA complex with the susceptibility to ASSD.
Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). However, their role ...remains unclear, and only 7–23% of these patients develops clinically overt vasculitis. We aimed to investigate the clinical, serological, and radiological features and prognosis of anti-MPO-positive interstitial lung disease (ILD) patients. Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clinical data, lung function testing, chest high-resolution computed tomography (HRCT) pattern, and survival were recorded. Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the patients’ survival. In fact, while the 52-week survival of the overall population was 71.4 ± 7.5%, significantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7 and 41.5% of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. A careful clinical history and evaluation should always be performed in ILD patients with anti-MPO antibodies to quickly identify patients who are developing a systemic rheumatic disease.
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